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Page 1: Kreb S  Cycle
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Ch 5: Membrane Ch 5: Membrane DynamicsDynamics

Cell membrane structures and functionsCell membrane structures and functions– Membranes form fluid body compartmentsMembranes form fluid body compartments– Membranes as barriers and gatekeepersMembranes as barriers and gatekeepers– How products move across membranesHow products move across membranes

• i.e., methods of transporti.e., methods of transport

– Distribution of water and solutes in cells & Distribution of water and solutes in cells & the bodythe body

– Chemical and electrical imbalancesChemical and electrical imbalances– Membrane permeability and changesMembrane permeability and changes

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Law of Mass Balance

• Most simply, ins = Most simply, ins = outsouts

• Homeostasis is Homeostasis is not the same as not the same as equilibriumequilibrium– E.g., membrane E.g., membrane

potentialspotentials

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Membrane Membrane – – 2 Meanings!2 Meanings!

• Epithelial membranesEpithelial membranes

vs.vs.• Cell membranes and Cell membranes and

Membranes around Membranes around organellesorganelles

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Cell Membrane Structure: Fluid Mosaic ModelCell Membrane Structure: Fluid Mosaic Model

Thickness ~ 8nm

PLsCholesterolProteins: peripheral (associated) or integral

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Membrane Membrane ProteinsProteins

IntegralIntegral((

Membrane-spanningMembrane-spanning or intrinsic or intrinsic))

• Can span membrane Can span membrane several timesseveral times

• Either move around or Either move around or are kept in place by are kept in place by cytoskeleton proteinscytoskeleton proteins

Allows for cell polarityAllows for cell polarity

AssociatedAssociated (peripheral or (peripheral or extrinsic)extrinsic)

• Loosely bound to Loosely bound to membranemembrane

• Enzymes and Enzymes and structural proteinsstructural proteins

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Other Phospholipid Other Phospholipid Behaviors in HBehaviors in H22O:O:

• Phospholipid bilayerPhospholipid bilayer

• MicelleMicelle– Role in digestion and Role in digestion and

absorption of fats in absorption of fats in GI tractGI tract

• LiposomeLiposome– Larger, bilayer, hollow Larger, bilayer, hollow

center with aqueous center with aqueous corecore Clinical relevance?

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Movement across Movement across MembraneMembrane

Membrane permeability varies for Membrane permeability varies for different different moleculesmolecules & & cell typescell types

Two movement categories:Two movement categories:

• Passive Passive and and

• ActiveActive

depends on??

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Diffusion Process (Passive)

Fig 5-5

•Uses energy of concentration Uses energy of concentration gradientgradient•Net movement until state of Net movement until state of equilibrium reached (no more equilibrium reached (no more conc. gradient) conc. gradient) •Direct correlation to temperature Direct correlation to temperature (why?)(why?)•Indirect correlation to molecule Indirect correlation to molecule sizesize•Slower with increasing distanceSlower with increasing distance•Lipophilic molecules can difuse Lipophilic molecules can difuse through the phospholipid bilayerthrough the phospholipid bilayer

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Time for diffusion to progress to given distance ~ to distance squared

diffusion over 100 m takes 5 sec.

diffusion over 200 m takes ??

diffusion over 400 m takes ??

diffusion over 800 m takes ??

Diffusion effective only over short distances!

Distance – Time Relationship

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Fick’s law of Diffusion (p 135)

surface area x conc. gradient

membrane resistance x membrane thickness

rate ofdiffusion

=

depends on size and lipid-solubility of molecule and composition of lipid bilayer

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Membrane Proteins

Fig 5-7

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Protein-Mediated Transport

• More selectiveMore selective– Active or PassiveActive or Passive

• Membrane ProteinsMembrane Proteins– StructuralStructural– EnzymesEnzymes– ReceptorsReceptors– Transporters (allows Specificity, Transporters (allows Specificity,

Competition, Saturation p 145)Competition, Saturation p 145)• ChannelChannel• GatedGated

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TransportersTransporters

Cell Membrane Regulates Exchange with Cell Membrane Regulates Exchange with EnvironmentEnvironment

Many molecules use transporters to Many molecules use transporters to cross cell membrane. cross cell membrane. Why?Why? Examples ?Examples ?

Two categories of transporter proteinsTwo categories of transporter proteins

1.1. Channel proteinsChannel proteins (rapid but not as (rapid but not as selective – for small molecules only, e.g., selective – for small molecules only, e.g., water and ions)water and ions)

2.2. Carrier proteinsCarrier proteins (slower but very (slower but very selective – also works for large selective – also works for large molecules)molecules)

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1. Channel Proteins1. Channel Proteins• For small molecules such For small molecules such

as ??as ??

• Aquaporin; plus > 100 ion Aquaporin; plus > 100 ion channelschannels

• Selectivity based on size Selectivity based on size & charge of molecule& charge of molecule

• All have gate regionAll have gate region

– OpenOpen

– GatedGated

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Open Channels vs. Open Channels vs. Gated Gated ChannelsChannels

= pores= pores

Have gates, but gates Have gates, but gates are open most of are open most of the time.the time.

Also referred to as Also referred to as “leak channels”.“leak channels”.

Gates closed most of the Gates closed most of the timetime

Chemically gated Chemically gated channelschannels (controlled by (controlled by messenger molecule or ligand)messenger molecule or ligand)

Voltage gated channelsVoltage gated channels (controlled by electrical state of (controlled by electrical state of cell)cell)

Mechanically gated Mechanically gated channelschannels (controlled by (controlled by physical state of cell: temp.; physical state of cell: temp.; stretching of cell membrane etc.)stretching of cell membrane etc.)

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2. Carrier Proteins2. Carrier Proteins

• Never form direct connection Never form direct connection between ECF and ICF – 2 between ECF and ICF – 2 gates!gates!

• Bind molecules and change Bind molecules and change conformationconformation

• Used for small organic Used for small organic molecules molecules (such as?)(such as?)

• Ions may use channels or Ions may use channels or carrierscarriers

• Rel. slow (1,000 to 1 Mio / Rel. slow (1,000 to 1 Mio / sec)sec)

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CotransportCotransportSymportSymport• Molecules are carried Molecules are carried

in same directionin same direction

• Examples: Glucose Examples: Glucose and Na and Na++

AntiportAntiport• Molecules are carried Molecules are carried

in opposite directionin opposite direction

• Examples: NaExamples: Na++/K/K++ pumppump

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Facilitated Diffusion Facilitated Diffusion (as (as a form of carrier mediated a form of carrier mediated transport)transport)

Some characteristics same as simple Some characteristics same as simple diffusion diffusion

but also:but also:• specificityspecificity• competitioncompetition• saturationsaturation

Figs 5-18/20

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Active TransportActive Transport

• Movement from low conc. Movement from low conc. to high conc.to high conc.

• ATP neededATP needed

• Creates state of Creates state of disdisequilibrium equilibrium

• 11oo (direct) active (direct) active transport transport – ATPases or “pumpsATPases or “pumps” ”

(uniport and antiport)– (uniport and antiport)– examples? examples?

• 22o o (indirect) active (indirect) active transporttransport – Symport and antiportSymport and antiport

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11oo (Direct) Active (Direct) Active Transport Transport

• ATP energy directly fuels transportATP energy directly fuels transport

• Most important example: NaMost important example: Na++/K/K++ pump = pump = sodium-potassium ATPasesodium-potassium ATPase (uses up to 30% of (uses up to 30% of cell’s ATP)cell’s ATP)

• Establishes Na+ Establishes Na+ conc. gradient conc. gradient EEpot.pot. can be can be harnessed for harnessed for other cell other cell functionsfunctions

ECF: high [Na+], low [K+]

ICF: high [K+], low [Na+]

Fig 5-16

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Mechanism of the Na+/K+-ATPase

start

Fig 5-17

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22oo (Indirect) Active (Indirect) Active Transport Transport • Indirect ATP use: Indirect ATP use: uses Euses Epot.pot.

stored in concentration stored in concentration gradientgradient (of Na (of Na++ and K and K++))

• Coupling of ECoupling of Ekinkin of one of one molecule with movement molecule with movement of another moleculeof another molecule

• Example: NaExample: Na++ / Glucose / Glucose symportersymporter

– other examplesother examples

• 2 mechanisms for Glucose 2 mechanisms for Glucose transporttransport

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Body Fluid Body Fluid CompartmentsCompartments

IC fluidIC fluid EC fluidEC fluid

Interstitial fluidInterstitial fluid plasmplasmaa

Relatively free exchange

Exchangemuch moreselective;

Why ?

Fig 5-13

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Body Fluid Compartments:

ECF ICF

Critical Thinking Question

What properties should a molecule have to be used as marker for one of the fluid compartments? Do total H2O; total EC and plasma. Then, how do you figure out ICF and interstitial fluid?

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Vesicular TransportVesicular Transport

Movement of Movement of macromoleculesmacromolecules across across cell membrane:cell membrane:

1.1. Phagocytosis (specialized cells Phagocytosis (specialized cells only)only)

2.2. EndocytosisEndocytosis– PinocytosisPinocytosis– Receptor mediated endocytosisReceptor mediated endocytosis– (Caveolae) Potocytosis(Caveolae) Potocytosis

3.3. ExocytosisExocytosis

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1. Phagocytosis1. Phagocytosis• Requires energy Requires energy

• Cell engulfs particle into vesicle via Cell engulfs particle into vesicle via pseudopodia formationpseudopodia formation

• E.g.:E.g.: some WBCs some WBCs engulf bacteriaengulf bacteria

• Vesicles formed are much larger than Vesicles formed are much larger than those formed by endocytosisthose formed by endocytosis

• Phagosome fuses with lysosomes Phagosome fuses with lysosomes ? ? (see Fig. 5-23)(see Fig. 5-23)

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2. Endocytosis2. Endocytosis• Requires energy Requires energy

• No pseudopodia - Membrane surface No pseudopodia - Membrane surface indentsindents

• Smaller vesiclesSmaller vesicles

• Nonselective:Nonselective: Pinocytosis Pinocytosis for fluids & for fluids & dissolved substancesdissolved substances

• Selective:Selective:– Receptor Mediated EndocytosisReceptor Mediated Endocytosis via clathrin-via clathrin-

coated pitscoated pits - - Example: LDL cholesterol and Example: LDL cholesterol and Familial Hypercholesterolemia Familial Hypercholesterolemia

– PodocytosisPodocytosis via caveolae via caveolae

Fig 5-24

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3. Exocytosis3. ExocytosisIntracellular vesicle fuses with membrane

Requires energy (ATP) and Ca2+

Examples: large lipophobic molecule secretion; receptor insertion; waste removal

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Movement through Movement through Epithelia: Epithelia: Transepithelial transportUses combination of active and passive transportUses combination of active and passive transport

Molecule must Molecule must cross two cross two phospholipid phospholipid

bilayers bilayers

Apical and basolateral cell membranes have Apical and basolateral cell membranes have different proteinsdifferent proteins::NaNa++- glucose transporter on apical membrane- glucose transporter on apical membraneNaNa++/K/K++-ATPase only on basolateral membrane-ATPase only on basolateral membrane

Fig 5-26

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Transcytosis

• Endocytosis Endocytosis vesicular transport vesicular transport exocytosis exocytosis

• Moves large proteins intactMoves large proteins intact

• Examples: Examples: – Absorption of maternalAbsorption of maternal

antibodies fromantibodies from breast milkbreast milk

– Movement of proteins Movement of proteins across capillary across capillary endotheliumendothelium

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Distribution of Solutes in Body

Depends onDepends on• selective permeability of cell selective permeability of cell

membranemembrane• transport mechanisms availabletransport mechanisms available

Water is in osmotic equilibrium (free Water is in osmotic equilibrium (free movement across membranes)movement across membranes)

Ions and most solutes are in chemical Ions and most solutes are in chemical disequilibrium (e.g., Na-K ATPase disequilibrium (e.g., Na-K ATPase Pump)Pump)

Electrical disequilibrium between ECF Electrical disequilibrium between ECF and ICFand ICF

Fig 5-33

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OsmosisMovement of water down its

concentration gradient.

Osmotic pressure

Opposes movement of water across membrane

Water moves freely in body until osmotic equilibrium is reached

Compare to Fig. 5-29

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Molarity vs. Osmolarity

In chemistry:In chemistry:• Mole / LMole / L• Avogadro’s # / LAvogadro’s # / L

In PhysiologyIn Physiology

Important is not # of Important is not # of molecules / L butmolecules / L but

# of particles / L: # of particles / L: osmol/L or OsMosmol/L or OsM

Why?Why?

Osmolarity takes into account dissociation (solubility) of molecules in solutionOsmolality = OsM/Kg of sol’n

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Convert Molarity to Osmolarity

Osmolarity = # of particles / L of solutionOsmolarity = # of particles / L of solution

• 1 M glucose = 1 OsM glucose1 M glucose = 1 OsM glucose

• 1 M NaCl = 2 OsM NaCl1 M NaCl = 2 OsM NaCl

• 1 M MgCl1 M MgCl22 = 3 OsM MgCl = 3 OsM MgCl22

• Osmolarity of human body ~ 300 mOsMOsmolarity of human body ~ 300 mOsM

• Compare isosmotic, hyperosmotic, Compare isosmotic, hyperosmotic, hyposmotic (p 156)hyposmotic (p 156)

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Tonicity

• Physiological term describing how Physiological term describing how cell volume changes if cell placed cell volume changes if cell placed in the solutionin the solution

• Always comparative. Has no units.Always comparative. Has no units.– Isotonic sol’n = No change in cellIsotonic sol’n = No change in cell

– Hypertonic sol’n = cell shrinksHypertonic sol’n = cell shrinks

– Hypotonic = cell expandsHypotonic = cell expands

• Depends not just on osmolarity but Depends not just on osmolarity but on on nature of solutes and nature of solutes and permeability of membranepermeability of membrane

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Penetrating vs. Nonpenetrating Solutes• Penetrating solute: can enter cell Penetrating solute: can enter cell

(glucose, urea)(glucose, urea)

• Nonpenetrating solutes: cannot Nonpenetrating solutes: cannot enter cell (sucrose, NaCl*)enter cell (sucrose, NaCl*)

• Determine relative conc. of Determine relative conc. of nonpenetrating solutes in nonpenetrating solutes in solution and in cell to determine solution and in cell to determine tonicity.tonicity.– Water will move to dilute nonpenetrating Water will move to dilute nonpenetrating

solutessolutes– Penetrating solutes will distribute to Penetrating solutes will distribute to

equilibriumequilibriumFig 5-30

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IV Fluid Therapy

2 different purposes:2 different purposes:– Get fluid into dehydrated cells orGet fluid into dehydrated cells or– Keep fluid in extra-cellular Keep fluid in extra-cellular

compartmentcompartment

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Electrical Disequilibrium and Resting Membrane Potential (pp.156-163) will be covered at the beginning of Ch 8

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Which of the following is a way for solutes in a aqueous solution to move from an area of high solute concentration to an area of low solute concentration?

A.A. Facilitated diffusionFacilitated diffusion

B.B. OsmosisOsmosis

C.C. Active transportActive transport

D.D. A and BA and B

E.E. None of theseNone of these

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Which of the following defines the term specificity?

A. movement of molecules by the use of vesicles

B. the energy required to move molecules

C. a group of carrier proteins operating at their maximum rate

D. carrier transport of a group of closely related molecules

E. none of these

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Water will always move from ___________ situations to _______ situations.

A.A. Hyperosmotic, hyposmoticHyperosmotic, hyposmotic

B.B. Hyposmotic, hyperosmoticHyposmotic, hyperosmotic

C.C. Hyposmotic, isosmoticHyposmotic, isosmotic

D.D. Hyperosmotic, isosmoticHyperosmotic, isosmotic

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Which of the following pairs of molecular characteristics favors diffusion through the cell membrane?

A.A. Large, polarLarge, polar

B.B. Large, non-polarLarge, non-polar

C.C. Small, polarSmall, polar

D.D. Small, non-polarSmall, non-polar

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Which of the following is a way for solutes in a aqueous solution to move from an area of high solute concentration to an area of low solute concentration?

A.A. Facilitated diffusionFacilitated diffusion

B.B. OsmosisOsmosis

C.C. Active transportActive transport

D.D. A and BA and B

E.E. None of theseNone of these